RECRUITING

A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-1)

Conditions

Psychosis Associated With Alzheimer's Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase 3, 38-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study in subjects with psychosis associated with Alzheimer's Disease. The primary objective of the study is to evaluate relapse prevention in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo. The secondary objectives of the study are to evaluate the time from randomization to discontinuation for any reason and safety and tolerability in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared to placebo.

Official Title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Relapse Prevention Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease

Quick Facts

Study Start:2022-08-23

Study Completion:2026-10-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05511363

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:55 Years to 90 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Is aged 55 to 90 years, inclusive, at Screening 2. Can understand the nature of the study and protocol requirements and provide a signed informed consent form before any study assessments are performed. If the subject is deemed not competent to provide consent, the following requirements for consent must be met. 1. The subject's legally acceptable representative or caregiver/study partner, if local regulations allow, must provide informed consent 2. The subject must provide informed assent 3. Meets clinical criteria for possible or probable Alzheimer's Disease 4. Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening. 5. Living at the same home or residential assisted-living facility for a minimum of six weeks before Screening 6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver (spends approximately 10 hours/week with the subject) that is willing to: 1. Attend all visits and report on subject's status 2. Oversee subject compliance with medication and study procedures 3. Participate in the study assessments and provide informed consent to participate in the study 7. History of psychotic symptoms (meeting International Psychogeriatric Association \[IPA\] criteria) for at least 2 months prior to Screening. 8. Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) at Screening and Baseline. CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions. 9. Subjects are required to meet at least one of the following criteria at Screening and Baseline: 1. Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR 2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items. 10. Mini-Mental State Examination (MMSE) score of 8 to 22, inclusive, at Screening 11. If the subject is taking a cholinesterase inhibitor and/or memantine, they must have been on a stable dose for 6 weeks prior to Screening and be willing to maintain a stable dose for the duration of the study. 12. Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements 13. BMI must be within 18 to 40 kg/m2 inclusive 14. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matching placebo. Sperm donation is not allowed for 30 days after the final dose of the IMP or matching placebo.	1. Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia 2. History of major depressive episode with psychotic features during the 12 months prior to Screening 3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder 4. Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular or oncologic disease, or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results 5. Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of \<60 mL/min/1.73 m2 6. History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke 7. History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope 8. Any of the following: 1. New York Heart Association Class 2 congestive heart failure 2. Grade 2 or greater angina pectoris 3. Sustained ventricular tachycardia 4. Ventricular fibrillation 5. Torsade de pointes 6. Implantable cardiac defibrillator 9. Myocardial infarction within the 6 months prior to Screening 10. Personal or family history of symptoms of long QT syndrome as evaluated by the investigator 11. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results 12. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator 13. For males only, any one of the following: 1. History of bladder stones 2. History of recurrent urinary tract infections 3. Serum prostate specific antigen (PSA) \> 10 ng/mL at Screening 4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6 5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 14. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months 15. Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS 16. Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening 17. Urine toxicology screen is positive substances other than cannabis or benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor 18. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate) 1. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted 2. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening. If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor. 19. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements 20. Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening; antigen or PCR local testing can be done at the discretion of the Investigator 21. Unable to taper and discontinue a concomitant medication that would preclude participation in the study 22. Prior exposure to KarXT 23. Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium 24. Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening or has participated in more than 2 clinical studies in the past year

Inclusion Criteria

Exclusion Criteria

1. Is aged 55 to 90 years, inclusive, at Screening
2. Can understand the nature of the study and protocol requirements and provide a signed informed consent form before any study assessments are performed. If the subject is deemed not competent to provide consent, the following requirements for consent must be met.
1. The subject's legally acceptable representative or caregiver/study partner, if local regulations allow, must provide informed consent
2. The subject must provide informed assent
3. Meets clinical criteria for possible or probable Alzheimer's Disease
4. Has a Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan of the brain (completed within the past 5 years) taken during or subsequent to the onset of dementia to rule out other central nervous system (CNS) disease that could account for the dementia syndrome. If not available, a non-contrast brain MRI or non-contrast head CT must be done during screening.
5. Living at the same home or residential assisted-living facility for a minimum of six weeks before Screening
6. Capable of self-locomotion (alone or with the aid of an assistive device) and have an identified or proxy caregiver (spends approximately 10 hours/week with the subject) that is willing to:
1. Attend all visits and report on subject's status
2. Oversee subject compliance with medication and study procedures
3. Participate in the study assessments and provide informed consent to participate in the study
7. History of psychotic symptoms (meeting International Psychogeriatric Association \[IPA\] criteria) for at least 2 months prior to Screening.
8. Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) at Screening and Baseline. CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions.
9. Subjects are required to meet at least one of the following criteria at Screening and Baseline:
1. Moderate to severe delusions, defined as Neuropsychiatric Inventory-Clinician (NPI-C): Delusions domain score of ≥2 on two of the eight items OR
2. Moderate to severe hallucinations, defined as NPI-C: Hallucinations domain score of ≥ 2 on two of the seven items.
10. Mini-Mental State Examination (MMSE) score of 8 to 22, inclusive, at Screening
11. If the subject is taking a cholinesterase inhibitor and/or memantine, they must have been on a stable dose for 6 weeks prior to Screening and be willing to maintain a stable dose for the duration of the study.
12. Subject is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements
13. BMI must be within 18 to 40 kg/m2 inclusive
14. Female subjects must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP), or men whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (e.g., 30 days) after the last dose of IMP or matching placebo. Sperm donation is not allowed for 30 days after the final dose of the IMP or matching placebo.

1. Psychotic symptoms that are primarily attributable to a condition other than the Alzheimer's Disease causing dementia
2. History of major depressive episode with psychotic features during the 12 months prior to Screening
3. History of a diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder
4. Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, cardiovascular or oncologic disease, or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results
5. Significant or severe renal impairment based on a screening cutoff for Estimated Glomerular Filtration Rate (eGFR) of \<60 mL/min/1.73 m2
6. History of ischemic stroke within 12 months prior to Screening or any evidence of hemorrhagic stroke
7. History of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, unstable thyroid function, or unexplained syncope
8. Any of the following:
1. New York Heart Association Class 2 congestive heart failure
2. Grade 2 or greater angina pectoris
3. Sustained ventricular tachycardia
4. Ventricular fibrillation
5. Torsade de pointes
6. Implantable cardiac defibrillator
9. Myocardial infarction within the 6 months prior to Screening
10. Personal or family history of symptoms of long QT syndrome as evaluated by the investigator
11. Human immunodeficiency virus, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or liver function tests results
12. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the investigator
13. For males only, any one of the following:
1. History of bladder stones
2. History of recurrent urinary tract infections
3. Serum prostate specific antigen (PSA) \> 10 ng/mL at Screening
4. An International Prostate Symptom Score (IPSS) of 5 (almost always) on items 1, 3, 5, or 6
5. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9
14. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months
15. Risk of suicidal behavior during the study as determined by clinical assessment and/ or C-SSRS
16. Clinically significant abnormal finding on the physical examination, electrocardiogram, or clinical laboratory results at Screening
17. Urine toxicology screen is positive substances other than cannabis or benzodiazepines (both cannabis and short-or medium-acting benzodiazepines are allowed in limited quantities during the study) unless approval has been given by the Medical Monitor
18. Recent history of receiving monoamine oxidase inhibitors, anticonvulsants (e.g., lamotrigine, divalproex), lithium, tricyclic antidepressants (e.g., imipramine, desipramine), or any other psychoactive medications except for as-needed anxiolytics (e.g., lorazepam, chloral hydrate)
1. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors taken at a stable dose for at least 8 weeks prior to Screening may be permitted
2. Mirtazapine or trazodone may be used as a hypnotic if started at least 8 weeks prior to Screening. If needed, an extension (up to two weeks) of the Screening Period may be allowed with approval of the Sponsor/Medical Monitor.
19. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor, subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/ Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
20. Positive test for coronavirus (COVID-19) within 2 weeks before or at Screening; antigen or PCR local testing can be done at the discretion of the Investigator
21. Unable to taper and discontinue a concomitant medication that would preclude participation in the study
22. Prior exposure to KarXT
23. Experienced any significant adverse events due to trospium, including a known hypersensitivity to trospium
24. Participation in another clinical study in which the subject received an experimental or investigational drug within 3 months before Screening or has participated in more than 2 clinical studies in the past year

Contacts and Locations

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286

Clinical.Trials@bms.com

First line of the email MUST contain the NCT# and Site #.

CONTACT

Principal Investigator

Bristol-Myers Squibb

STUDY_DIRECTOR

Bristol-Myers Squibb

Study Locations (Sites)

Tilda Alabama - PPDS

Homewood, Alabama, 35209-6809

United States

IMA Clinical Research - Phoenix - PPDS

Phoenix, Arizona, 85012-2836

United States

ATP Clinical Research

Costa Mesa, California, 92626

United States

Asclepes Research

Encino, California, 91436-2201

United States

Local Institution - 1031

Irvine, California, 92612-1246

United States

Sunwise Clinical Research, LLC - IVY - PPDS

Lafayette, California, 94549

United States

SC3 Research - Pasadena

Pasadena, California, 91105-3132

United States

Local Institution - 1047

San Marcos, California, 92069-3595

United States

Colorado Springs Neurological Associates

Colorado Springs, Colorado, 80907-5302

United States

Ki Health Partners LLC DBA New England Institute for Clinical Research

Stamford, Connecticut, 06905-1206

United States

South Florida Neurology Associates

Boca Raton, Florida, 33487-2768

United States

Envision Trials LLC

Bonita Springs, Florida, 34134-4154

United States

Local Institution - 1015

Bradenton, Florida, 34209-4687

United States

K2 Medical Research - Winter Garden

Clermont, Florida, 34711-5933

United States

Arrow Clinical Trials

Daytona Beach, Florida, 32117-5532

United States

Betancourt Research Services

Doral, Florida, 33172-2638

United States

Local Institution - 1052

Hialeah, Florida, 33010

United States

United Research Institute

Hialeah, Florida, 33012-5826

United States

Local Institution - 1024

Hialeah, Florida, 33012-5884

United States

Coral Clinic Research

Homestead, Florida, 33032

United States

K2 Medical Research - Maitland

Maitland, Florida, 32751-5669

United States

San Marcus Research Clinic Inc

Miami Lakes, Florida, 33014-5602

United States

Ocean Blue Medical Research Center Inc

Miami Springs, Florida, 33166-5260

United States

Premier Clinical Research Institute - Miami - ClinEdge - PPDS

Miami, Florida, 33122-1335

United States

Global Medical Institutes, LLC - Miami - ClinEdge - PPDS

Miami, Florida, 33125-3724

United States

Miami Jewish Health Systems

Miami, Florida, 33137

United States

Allied Biomedical Research Institute

Miami, Florida, 33155-4630

United States

Novel Clinical Research Center, LLC.

Miami, Florida, 33173-1474

United States

ONHEALTH Research Center

Miami, Florida, 33186-5882

United States

Local Institution - 1027

Ocala, Florida, 34470-6657

United States

Emerald Coast Center for Neurological Disorders

Pensacola, Florida, 32504-8608

United States

Suncoast Neuroscience Associates Inc

Saint Petersburg, Florida, 33713-8844

United States

Local Institution - 1050

Tampa, Florida, 33606

United States

K2 Medical Research - Tampa

Tampa, Florida, 33607-4629

United States

Local Institution - 1040

The Villages, Florida, 32159-8986

United States

Research Network America

Berwyn, Illinois, 60402-2173

United States

Feinstein Institute For Medical Research

Manhasset, New York, 11030-3816

United States

Local Institution - 1030

New York, New York, 10016

United States

Local Institution - 1051

New York, New York, 10032-3720

United States

Columbia University Medical Center

New York, New York, 10032

United States

Richmond Behavioral Associates

Staten Island, New York, 10314-1607

United States

Stony Brook University Medical Center

Stony Brook, New York, 11794-0001

United States

Five Towns Neurology, PC

Woodmere, New York, 11598-1739

United States

Local Institution - 1003

Canton, Ohio, 44718

United States

Local Institution - 1028

Oklahoma City, Oklahoma, 73104-5007

United States

Local Institution - 1016

Oklahoma City, Oklahoma, 73112-8766

United States

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104-5034

United States

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425

United States

KCA Neurology, PLLC

Franklin, Tennessee, 37067-5922

United States

North Pointe Psychiatry - Flower Mound

Flower Mound, Texas, 75028-2011

United States

Beautiful Minds

Frisco, Texas, 75034-6262

United States

Clinical Trial Network - 7080 Southwest Fwy

Houston, Texas, 77074-2085

United States

Collaborators and Investigators

Sponsor: Karuna Therapeutics

Bristol-Myers Squibb, STUDY_DIRECTOR, Bristol-Myers Squibb

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-08-23

Study Completion Date2026-10-05

Study Record Updates

Study Start Date2022-08-23

Study Completion Date2026-10-05

Terms related to this study

Additional Relevant MeSH Terms

Psychosis Associated With Alzheimer's Disease